Gene

Melanin

Phenotype

Function (biology)

Receptor

Melanocortin 1 receptor

Rhodopsin

Human skin

Melanoma

Melanocyte

Melanocortin

Retinal

Opsin

Cancer research

Genetics

Biochemistry

Biology

Cell biology

Proceedings of the National Academy of Sciences

Significance This study expands understanding of opsin 3 (OPN3) function and of skin pigmentation. The findings presented here reveal that the nonvisual OPN3 modulates the pigmentation of human epidermal melanocytes—the melanin-producing cells of the skin—by controlling the activity of the main pigmentation receptor, melanocortin 1 receptor (MC1R). The study identifies an OPN3 function in regulating human skin pigmentation via a unique molecular mechanism; it also reveals a regulatory mechanism for MC1R in melanocytes. These results advance our understanding of nonvisual opsins and their extraocular role; they also represent a paradigm for OPN3 function via modulation of MC1R’s activity. These findings set the stage for future investigations of OPN3 function in other tissues.

Human nonvisual opsin 3 regulates pigmentation of epidermal melanocytes through functional interaction with melanocortin 1 receptor